RT Journal Article
SR Electronic
T1 LIF Drives Neural Remodeling in Pancreatic Cancer and Offers a New Candidate Biomarker
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 909
OP 921
DO 10.1158/0008-5472.CAN-15-2790
VO 78
IS 4
A1 Bressy, Christian
A1 Lac, Sophie
A1 Nigri, Jérémy
A1 Leca, Julie
A1 Roques, Julie
A1 Lavaut, Marie-Nöelle
A1 Secq, Véronique
A1 Guillaumond, Fabienne
A1 Bui, Thi-Thien
A1 Pietrasz, Daniel
A1 Granjeaud, Samuel
A1 Bachet, Jean-Baptiste
A1 Ouaissi, Mehdi
A1 Iovanna, Juan
A1 Vasseur, Sophie
A1 Tomasini, Richard
YR 2018
UL http://cancerres.aacrjournals.org/content/78/4/909.abstract
AB Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive stroma and pathogenic modifications to the peripheral nervous system that elevate metastatic capacity. In this study, we show that the IL6-related stem cell–promoting factor LIF supports PDAC-associated neural remodeling (PANR). LIF was overexpressed in tumor tissue compared with healthy pancreas, but its receptors LIFR and gp130 were expressed only in intratumoral nerves. Cancer cells and stromal cells in PDAC tissues both expressed LIF, but only stromal cells could secrete it. Biological investigations showed that LIF promoted the differentiation of glial nerve sheath Schwann cells and induced their migration by activating JAK/STAT3/AKT signaling. LIF also induced neuronal plasticity in dorsal root ganglia neurons by increasing the number of neurites and the soma area. Notably, injection of LIF-blocking antibody into PDAC-bearing mice reduced intratumoral nerve density, supporting a critical role for LIF function in PANR. In serum from human PDAC patients and mouse models of PDAC, we found that LIF titers positively correlated with intratumoral nerve density. Taken together, our findings suggest LIF as a candidate serum biomarker and diagnostic tool and a possible therapeutic target for limiting the impact of PANR in PDAC pathophysiology and metastatic progression.Significance: This study suggests a target to limit neural remodeling in pancreatic cancer, which contributes to poorer quality of life and heightened metastatic progression in patients. Cancer Res; 78(4); 909–21. ©2017 AACR.